Browsing by Subject "COMPLEXES"

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  • Celaya, Christian A.; Orozco-Ic, Mesias; Dimitrova, Maria; Wirz, Lukas N.; Sundholm, Dage (2020)
    We propose a novel class of gold-containing molecules, which have been designed using conjugated carbon structures as templates. The sp-hybridized carbons of C-2 moieties are replaced with a gold atom and one of the adjacent carbons is replaced by nitrogen. Applying the procedure to hexadehydro[12]annulene yields the well-known cyclic trinuclear gold(i) carbeniate complex. Planar, tubular and cage-shaped complexes can be obtained by taking similar sp-hybridized carbon structures as the starting point.
  • Bogacheva, Mariia; Egorova, Anna; Slita, Anna; Maretina, Marianna; Baranov, Vladislav; Kiselev, Anton (2017)
    The major barriers for intracellular DNA transportation by cationic polymers are their toxicity, poor endosomal escape and inefficient nuclear uptake. Therefore, we designed novel modular peptide-based carriers modified with SV40 nuclear localization signal (NLS). Core peptide consists of arginine, histidine and cysteine residues for DNA condensation, endosomal escape promotion and interpeptide cross-linking, respectively. We investigated three polyplexes with different NLS content (10 mol%, 50 mol% and 90 mol% of SV40 NLS) as vectors for intranuclear DNA delivery. All carriers tested were able to condense DNA, to protect it from DNAase I and were not toxic to the cells. We observed that cell cycle arrest by hydroxyurea did not affect transfection efficacy of NLS-modified carriers which we confirmed using quantitative confocal microscopy analysis. Overall, peptide carrier modified with 90 mol% of SV40 NLS provided efficient transfection and nuclear uptake in non-dividing cells. Thus, incorporation of NLS into arginine-rich cross-linking peptides is an adequate approach to the development of efficient intranuclear gene delivery vehicles. (C) 2017 Elsevier Ltd. All rights reserved.
  • Bartkowski, Krzysztof; Dimitroya, Maria; Chmielewski, Piotr J.; Sundholm, Dage; Pawlicki, Milosz (2019)
    It is important to understand the aromatic properties and magnetically induced current densities of highly conjugated chromophores when one designs molecules with strongly delocalized electronic structure. The aromatic character can be modified by linearly extending the electron delocalization pathway of the triphyrin(2.1.1) skeleton with an annelated benzo[b]heterocycle fragment. Two-electron reduction of the extended triphyrin leads to an antiaromatic triphyrin(2.1.1) ring and an aromatic benzo[b]heterocycle subunit. Detailed information about the observed pathways and their strengths are obtained by performing current-density calculation.
  • Mattinen, Miika; Wree, Jan-Lucas; Stegmann, Niklas; Ciftyurek, Engin; El Achhab, Mhamed; King, Peter J.; Mizohata, Kenichiro; Räisänen, Jyrki; Schierbaum, Klaus D.; Devi, Anjana; Ritala, Mikko; Leskelä, Markku (2018)
    Heteroleptic bis(tert-butylimido)bis(N,N'-diisopropylacetamidinato) compounds of molybdenum and tungsten are introduced as precursors for atomic layer deposition of tungsten and molybdenum oxide thin films using ozone as the oxygen source. Both precursors have similar thermal properties but exhibit different growth behaviors. With the molybdenum precursor, high growth rates up to 2 angstrom/cycle at 300 degrees C and extremely uniform films are obtained, although the surface reactions are not completely saturative. The corresponding tungsten precursor enables saturative film growth with a lower growth rate of 0.45 angstrom/cycle at 300 degrees C. Highly pure films of both metal oxides are deposited, and their phase as well as stoichiometry can be tuned by changing the deposition conditions. The WO films the crystallize as gamma-WO3 at 300 degrees C and above, whereas films deposited at lower temperatures are amorphous. Molybdenum oxide can be deposited as either amorphous (= 325 degrees C) films. MoOr films are further characterized by synchrotron photoemission spectroscopy and temperature-dependent resistivity measurements. A suboxide MoOx film deposited at 275 degrees C is demonstrated to serve as an efficient hydrogen gas sensor at a low operating temperature of 120 degrees C.
  • Hernandez-Perez, Sara; Vainio, Marika; Kuokkanen, Elina; Sustar, Vid; Petrov, Petar; Forsten, Sofia; Paavola, Vilma; Rajala, Johanna; Awoniyi, Luqman O.; Sarapulov, Alexey; Vihinen, Helena; Jokitalo, Eija; Bruckbauer, Andreas; Mattila, Pieta K. (2020)
    In order to mount high-affinity antibody responses, B cells internalise specific antigens and process them into peptides loaded onto MHCII for presentation to T helper cells (T H cells). While the biochemical principles of antigen processing and MHCII loading have been well dissected, how the endosomal vesicle system is wired to enable these specific functions remains much less studied. Here, we performed a systematic microscopy-based analysis of antigen trafficking in B cells to reveal its route to the MHCII peptide-loading compartment (MIIC). Surprisingly, we detected fast targeting of internalised antigen into peripheral acidic compartments that possessed the hallmarks of the MIIC and also showed degradative capacity. In these vesicles, intemalised antigen converged rapidly with membrane-derived MHCII and partially overlapped with cathepsin-S and H2-M, both required for peptide loading. These early compartments appeared heterogenous and atypical as they contained a mixture of both early and late endosomal markers, indicating a specialized endosomal route. Together, our data suggest that, in addition to in the previously reported perinuclear late endosomal MIICs, antigen processing and peptide loading could have already started in these specialized early peripheral acidic vesicles (eMlIC) to support fast peptide-MHCII presentation. This article has an associated First Person interview with the first author of the paper.
  • Otto, Christian F.; Herzberger, Colin; Liu, Ming; Namyslo, Jan C.; Nieger, Martin; Freese, Tyll; Lederle, Felix; Hübner, Eike G.; Schmidt, Andreas (2020)
    The natural product punicine (Punica granatum) exists in two tautomeric forms, the cross-conjugated mesomeric betaine 1-(pyridinium-1-yl)-2-hydroxy-phenyl-5-olate and the conjugated mesomeric betaine 1-(pyridinium-1-yl)-5-hydroxy-phenyl-2-olate. Punicine as well as its picoline derivatives reacted with tris(pentafluorophenyl)borane exclusively at the 2'-olate group to form zwitterionic borates. Correspondingly, the 5'-dehydroxy derivate of punicine, the conjugated heterocyclic mesomeric betaine 1-(pyridinium-1-yl)-phenyl-2-olate and its picoline derivatives also gave borates, whereas analogous reactions of the cross-conjugated isomer 2'-dehydroxypunicine [1-(pyridinium-1-yl)-phenyl-3-olatel did not result in the formation of stable adducts. (C) 2020 Elsevier Ltd. All rights reserved.
  • Al-Hunaiti, Afnan; Abu-Radaha, Batool; Wraith, Darren; Repo, Timo (2022)
    Here, we disclose a new copper(i)-Schiff base complex series for selective oxidation of primary alcohols to aldehydes under benign conditions. The catalytic protocol involves 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO), N-methylimidazole (NMI), ambient air, acetonitrile, and room temperature. This system provides a straightforward and rapid pathway to a series of Schiff bases, particularly, the copper(i) complexes bearing the substituted (furan-2-yl)imine bases N-(4-fluorophenyl)-1-(furan-2-yl)methanimine (L2) and N-(2-fluoro-4-nitrophenyl)-1-(furan-2-yl)methanimine (L4) have shown excellent yields. Both benzylic and aliphatic alcohols were converted to aldehydes selectively with 99% yield (in 1-2 h) and 96% yield (in 16 h). The mechanistic studies via kinetic analysis of all components demonstrate that the ligand type plays a key role in reaction rate. The basicity of the ligand increases the electron density of the metal center, which leads to higher oxidation reactivity. The Hammett plot shows that the key step does not involve H-abstraction. Additionally, a generalized additive model (GAM, including random effect) showed that it was possible to correlate reaction composition with catalytic activity, ligand structure, and substrate behavior. This can be developed in the form of a predictive model bearing in mind numerous reactions to be performed or in order to produce a massive data-set of this type of oxidation reaction. The predictive model will act as a useful tool towards understanding the key steps in catalytic oxidation through dimensional optimization while reducing the screening of statistically poor active catalysis.
  • Valadbeigi, Younes; Kurten, Theo (2019)
    HClO4 is an important catalyst in organic chemistry, and also acts as a reservoir or sink species in atmospheric chlorine chemistry. In this study, we computationally investigate the interactions of Bronsted (H2SO4, HClO4, HNO3) and Lewis acids (BH3, BF3, BCl3, BBr3, B(OH)(3)) with HClO4 using the omega B97xD method and the aug-cc-pVDZ basis set. Different isomers of clusters with up to 4 molecules (tetramer) were optimized, and the most stable structures were determined. The enthalpies, Delta H, and Gibbs free energies, Delta G, of cluster formation were calculated in the gas phase at 298 K. Atoms in molecules (AIM) calculations find B-O bond critical points only in the (BH3)(n)HClO4 clusters, while formation of other clusters was based on hydrogen bonding interactions. (H2SO4)HClO4 and (B(OH)(3))HClO4, with formation enthalpies of -14.1 and -12.0 kcal mol(-1), were the most stable, and (BCl3)HClO4 with a formation enthalpy of -2.9 kcal mol(-1), was the least stable cluster among the dimers. Clustering of the Lewis and Bronsted acids with HClO4 enhanced its acidity, so that clustering of four HClO4 molecules and formation of (HClO4)(4) increases the acidity of HClO4 by about 35 kcal mol(-1). The most acidic dimer cluster found in the study was (BBr3)HClO4, with Delta H-acid of 275 kcal mol(-1); 26 kcal mol(-1) stronger than that of the HClO4 monomer.
  • Bösl, Korbinian; Ianevski, Aleksandr; Than, Thoa T.; Andersen, Petter I.; Kuivanen, Suvi; Teppor, Mona; Zusinaite, Eva; Dumpis, Uga; Vitkauskiene, Astra; Cox, Rebecca J.; Kallio-Kokko, Hannimari; Bergqvist, Anders; Tenson, Tanel; Merits, Andres; Oksenych, Valentyn; Bjørås, Magnar; Anthonsen, Marit W.; Shum, David; Kaarbø, Mari; Vapalahti, Olli; Windisch, Marc P.; Superti-Furga, Giulio; Snijder, Berend; Kainov, Denis; Kandasamy, Richard K. (2019)
    Viruses are one of the major causes of acute and chronic infectious diseases and thus a major contributor to the global burden of disease. Several studies have shown how viruses have evolved to hijack basic cellular pathways and evade innate immune response by modulating key host factors and signaling pathways. A collective view of these multiple studies could advance our understanding of virus-host interactions and provide new therapeutic perspectives for the treatment of viral diseases. Here, we performed an integrative meta-analysis to elucidate the 17 different host-virus interactomes. Network and bioinformatics analyses showed how viruses with small genomes efficiently achieve the maximal effect by targeting multifunctional and highly connected host proteins with a high occurrence of disordered regions. We also identified the core cellular process subnetworks that are targeted by all the viruses. Integration with functional RNA interference (RNAi) datasets showed that a large proportion of the targets are required for viral replication. Furthermore, we performed an interactome-informed drug re-purposing screen and identified novel activities for broad-spectrum antiviral agents against hepatitis C virus and human metapneumovirus. Altogether, these orthogonal datasets could serve as a platform for hypothesis generation and follow-up studies to broaden our understanding of the viral evasion landscape.
  • Blum, Markus; Gebhardt, Jacqueline; Papendick, Marius; Schlindwein, Simon H.; Nieger, Martin; Gudat, Dietrich (2018)
    Two N-heterocyclic phosphines with exocyclic SCN substituents were synthesised via metathesis of chlorophosphine precursors with KSCN and fully characterised. The crystallographic studies reveal that the products exhibit pronounced structural differences. The thiocyanato unit binds in one case via the nitrogen atom to yield a molecular structure with a slightly elongated P-N single bond and, in the other case, via the sulfur atom to form a structure that is best described as an ion pair and forms a one-dimensional coordination polymer in the crystal. DFT calculations suggest that the P-N and P center dot center dot center dot S interactions can be described as covalent and dative bonds, respectively, and that the structural differences correlate with the different cation stabilities of the individual phosphenium cation fragments.
  • Zippel, Christoph; Hassan, Zahid; Nieger, Martin; Bräse, Stefan (2020)
    A planar chiral dirhodium paddlewheel complex Rh-2(S-p-PCP)(4)based on the [2.2]paracyclophane has been synthesized for the challenging cyclopropanation of venylarene derivatives withtert-butyl alpha-diazo propionates. The homobimetallic rhodium catalyst relies on the high steric demand and rigidity of [2.2]paracyclophane that favors the cyclopropanation of 1-aryl substituted, 1,1-disubstituted and benzannulated alkenes over beta-hydride migration at room temperature with high diastereoselectivity.
  • Hassan, Alaa A.; Aly, Ashraf A.; Mohamed, Nasr K.; El Shaieb, Kamal M.; Makhlouf, Maysa M.; Abdelhafez, El-Shimaa M. N.; Bräse, Stefan; Nieger, Martin; Dalby, Kevin N.; Kaoud, Tamer S. (2019)
    A large number of natural products containing the propellane scaffold have been reported to exhibit cytotoxicity against several cancers; however, their mechanism of action is still unknown. Anticancer drugs targeting DNA are mainly composed of small planar molecule/s that can interact with the DNA helix, causing DNA malfunction and cell death. The aim of this study was to design and synthesize propellane derivatives that can act as DNA intercalators and/or groove binders. The unique structure of the propellane derivatives and their ability to display planar ligands with numerous possible geometries, renders them potential starting points to design new drugs targeting DNA in cancer cells. New substituted furo-imidazo[3.3.3]propellanes were synthesized via the reaction of substituted alkenylidene-hydrazinecarbothioamides with 2-(1,3-dioxo-2,3-dihydr- 1H-2-ylidene) propanedinitrile in tetrahydrofuran at room temperature. The structures of the products were confirmed by a combination of elemental analysis, NMR, ESI-MS, IR and single crystal X-ray analysis. Interestingly, 5c, 5d and 5f showed an ability to interact with Calf Thymus DNA (CT-DNA). Their DNA-binding mode was investigated using a combination of absorption spectroscopy, DNA melting, viscosity, CD spectroscopy measurements, as well as competitive binding studies with several dyes. Their cytotoxicity was evaluated against the NCI-60 panel of cancer cell lines. 5c, 5d and 5f exhibited similar anti-proliferative activity against the A549 non-small cell lung cancer (NSCLC) cell line. Further mechanistic studies revealed their ability to induce DNA damage in the A549 cell line, as well as apoptosis, evidenced by elevated Annexin V expression, enhanced caspase 3/7 activation and PARP cleavage. In this study, we present the potential for designing novel propellanes to provoke cytotoxic activity, likely through DNA binding-induced DNA damage and apoptosis.
  • Takala, Ninni; Siren, Heli; Jakl, Michal; Dytrtová, Jana Jaklová (2019)
    The azoles (represented by penconazole, cyproconazole, and tebuconazole in this study) are frequently used agrochemicals to protect various crops against mildew and fungi. They are considered as endocrine disruptors, because they block the biosynthesis (on the level of enzymes inhibition) of biochemicals with steroid structure. Besides targeted impacts, they can partly get into the soil with the rainfall or litter fall and influence/block the biosynthesis of sterols of non-target organisms. In this sense, the risk of disruption of rhizosphere plant-microbial symbiosis and dynamic processes in the soil solution by azoles is of high importance to be evaluated. We have developed an analytical methodology for determination of penconazole, cyproconazole, and tebuconazole in soil solution using capillary electrophoresis with a photodiode array detector at UV-214 nm and acidic electrolyte solution (pH 1.48). The results were also compared with mass spectrometric measurements using mu-TOF mass spectrometry. There approx. 90% of present azoles were bound in the soil solution matrix. The detection limit for these azoles is about 10(-7) mol dm(-3). Because of very low pK(a) of azoles, we have to consider deprotonation of azoles and consequently the high affinity to create complexes with cations. The majority of present azoles in soil solution might form neutral adducts with mono-cations, making them invisible in electrospray mass spectra. [GRAPHICS] .
  • Väyrynen, Katja; Hatanpää, Timo; Mattinen, Miika; Heikkilä, Mikko; Mizohata, Kenichiro; Meinander, Kristoffer; Räisänen, Jyrki; Ritala, Mikko; Leskelä, Markku (2018)
    In this paper, we introduce a new Co precursor for the atomic layer deposition (ALD) of Co metal and other Co containing materials. CoCl2(TMEDA) (TMEDA = N,N,N ',N '-tetramethylethylenediamine) is a diamine adduct of cobalt(II) chloride that is inexpensive and easy to synthesize, making it an industrially viable precursor. Furthermore, CoCl2(TMEDA) shows good volatility at reasonably low temperatures and is thermally stable up to a temperature of, similar to 300 degrees C. We also present a full ALD study for the deposition of CoO thin films using CoCl2(TMEDA) and water as precursors. The process was investigated within a temperature range of 225-300 degrees C. Saturation of the film growth with respect to both precursor pulse lengths was verified. According to X-ray diffraction, the films were a mixture of hexagonal and cubic CoO. No reflections corresponding to Co3O4 were detected. The hexagonal phase is characteristic to nanomaterials only and is not seen in bulk CoO. The crystal structure of the films could be tuned by temperature, water pulse lengths, and type of substrate material. The films deposited at 275 degrees C exhibited 1:1 Co:O stoichiometry and very high purity. The CoO films could be reduced to Co metal at an exceptionally low temperature of 250 degrees C in 10% forming gas. Continuity of the reduced Co films was improved when the CoO film was deposited on TiN instead of native oxide terminated Si. The Co content of a 50 nm reduced metal film was as high as 95 at. %, with negligible amounts of oxygen and hydrogen.
  • Burley, Jonathan C.; Motherwell, W. D. Sam; Maaranen, Janne; Ringwald, Markus (2007)
  • Spruit, Cindy; Wicklund, Anu; Wan, Xing; Skurnik, Mikael; Pajunen, Maria (2020)
    The lytic phage, fHe-Kpn01 was isolated from sewage water using an extended-spectrum beta-lactamase-producing strain of Klebsiella pneumoniae as a host. The genome is 43,329 bp in size and contains direct terminal repeats of 222 bp. The genome contains 56 predicted genes, of which proteomics analysis detected 29 different proteins in purified phage particles. Comparison of fHe-Kpn01 to other phages, both morphologically and genetically, indicated that the phage belongs to the family Podoviridae and genus Drulisvirus. Because fHe-Kpn01 is strictly lytic and does not carry any known resistance or virulence genes, it is suitable for phage therapy. It has, however, a narrow host range since it infected only three of the 72 tested K. pneumoniae strains, two of which were of capsule type KL62. After annotation of the predicted genes based on the similarity to genes of known function and proteomics results on the virion-associated proteins, 22 gene products remained annotated as hypothetical proteins of unknown function (HPUF). These fHe-Kpn01 HPUFs were screened for their toxicity in Escherichia coli. Three of the HPUFs, encoded by the genes g10, g22, and g38, were confirmed to be toxic.
  • Mendizabal, Fernando; Mera-Adasme, Raul; Xu, Wen-Hua; Sundholm, Dage (2017)
    Dye-sensitized solar-cell (DSSC) systems have been investigated by calculating light-absorption and electron-injection processes of the LD13 ([5,15-bis(2,6-(1,1-dimethylethyl)-phenyl)-10-4-dimethylaminophenylethynyl-20-4-carboxy phenylethynyl porphyrinato]zinc-(II)) and YD2-o-C8 ([5,15bis( 2,6-dioctoxyphenyl)-10-(bis(4-hexylphenyl)amino-20-4-carboxyphenylethynyl)porphyrinato]zinc-(II)) dyes adsorbed on a TiO2 cluster simulating the semiconductor. The binding energy of the dyes with the TiO2 clusters has been calculated at the density functional theory (DFT) level using the B3LYP and CAM-B3LYP functionals. The electronic excitation energies have been calculated at the time-dependent DFT (TDDFT) level for the dyes in the gas and solvent phase employing the B3LYP, CAM-B3LYP and BHLYP functionals. The calculated excitation energies have been compared to values obtained at the algebraic diagrammatic construction through second order (ADC(2)) level of theory. The TDDFT calculations with the B3LYP in tetrahydrofuran solvent with the dye and dye-TiO2 models yield excitation energies that agree well with the transitions in the experimental absorption spectra. Changes in the free energy for electron injection support the better performance of the dyes on the TiO2 clusters.
  • Habraken, Evi R. M.; van der Zee, Lars J. C.; van de Vrande, Koen N. A.; Jupp, Andrew R.; Nieger, Martin; Ehlers, Andreas W.; Slootweg, J. Chris (2019)
    Azophosphonium salts have a facile synthesis and can be readily tuned at the para position of the aryl group and at the phosphorus position with the use of bulky phosphines, leading to a range of coloured compounds. A relation between the Hammett sigma(+)(para) constant and the colour and P-31 NMR chemical shift was explored. The compounds were characterised by NMR spectroscopy, UV/Vis spectroscopy and single-crystal X-ray structure crystallography.
  • Valiev, R. R.; Cherepanov, V. N.; Baryshnikov, G. V.; Sundholm, D. (2018)
    A method for calculating the rate constants for internal-conversion (k(IC)) and intersystem-crossing (k(ISC)) processes within the adiabatic and Franck-Condon (FC) approximations is proposed. The applicability of the method is demonstrated by calculation of k(IC) and k(ISC) for a set of organic and organometallic compounds with experimentally known spectroscopic properties. The studied molecules were pyrromethene-567 dye, psoralene, hetero[8]circulenes, free-base porphyrin, naphthalene, and larger polyacenes. We also studied fac-Alq(3) and fac-Ir(ppy)(3), which are important molecules in organic light emitting diodes (OLEDs). The excitation energies were calculated at the multi-configuration quasi-degenerate second-order perturbation theory (XMC-QDPT2) level, which is found to yield excitation energies in good agreement with experimental data. Spin-orbit coupling matrix elements, non-adiabatic coupling matrix elements, Huang-Rhys factors, and vibrational energies were calculated at the time-dependent density functional theory (TDDFT) and complete active space self-consistent field (CASSCF) levels. The computed fluorescence quantum yields for the pyrromethene-567 dye, psoralene, hetero[8]circulenes, fac-Alq(3) and fac-Ir(ppy)(3) agree well with experimental data, whereas for the free-base porphyrin, naphthalene, and the polyacenes, the obtained quantum yields significantly differ from the experimental values, because the FC and adiabatic approximations are not accurate for these molecules.
  • Rehan, Shahid; Paavilainen, Ville O.; Jaakola, Veli-Pekka (2017)
    The human equilibrative nucleoside transporter-1 (hENT1) is important for the entry of anti-cancer and antiviral nucleoside analog therapeutics into the cell, and thus for their efficacy. Understanding of hENT1 structure -function relationship could assist with development of nucleoside analogs with better cellular uptake properties. However, structural and biophysical studies of hENT1 remain challenging as the hydrophobic nature of the protein leads to complete aggregation upon detergent-based membrane isolation. Here we report detergent-free reconstitution of the hENT1 transporter into styrene maleic acid co-polymer lipid particles (SMALPs) that form a native lipid disc. SMALP-purified hENT1, expressed in Sf9 insect cells binds a variety of ligands with a similar affinity as the protein in native membrane, and exhibits increased thermal stability compared to detergent-solubilized hENT1. hENT1-SMALPs purified using FLAG affinity M2 resin yielded similar to 0.4 mg of active and homogenous protein per liter of culture as demonstrated by ligand binding, size-exclusion chromatography and SDS-PAGE analyses. Electrospray ionization mass spectrometry (ESI-MS) analysis showed that each hENT1 lipid disc contains 16 phosphatidylcholine (PC) and 2 phosphatidylethanolamine (PE) lipid molecules. Polyunsaturated lipids are specifically excluded from the hENT1 lipid discs, possibly reflecting a functional requirement for a dynamic lipid environment. Our work demonstrates that human nucleoside transporters can be extracted and purified without removal from their native lipid environment, opening up a wide range of possibilities for their biophysical and structural studies. (C) 2017 Elsevier B.V. All rights reserved.